Cacti & Harmalas, any final word on safety?

[Grey Fox]

I'm not trying to beat a dead horse or anything. Just trying to understand better. But what do you think the benefit or "upside" to the combo might be? Is it just a matter of potentiating the cactus so that less cactus would be necessary or is there some added benefit beyond that to using the harmala?

 

[Elrik]

Starting very low on both and increasing both together could easily lead to surprises if you suddenly reach a point where the harmalas are finally effective and you took it with too much cactus. When working with a binary mixture its safest to take the potentiator drug in full dose from the start. For this reason I'd advise caution if considering only 100mg harmalas.
What I did to establish safe combination doses was to use the harmala dose I had been using with pharma [200mg rue manske crystals] and first do the harmalas just on their own to establish a baseline. I then repeated that harmala dose on subsequent occasions with fist very low, then increasing doses of cactus tea and then crystalline mescaline. The harmaline/harmine + cactus tea tests gave me some indication of just how much it boosted the potency and just how it changed the effects so when I started on harmaline/harmine + mescaline I used 200mg harmalas with 375mg snow white mescaline to good, but not over strong, effect.
My trip notes from that session ended with this summary:

Beyond previous unrefined 400 mg trial. In terms of visuals the peak was very nearly as high as the previous refined 500 mg assay but this was clear-headed and less mind fucking. No ego death. Still highly emotional. No nausea at all, no anorexia much past peak. The change from pure mescaline to this somewhat reminded me of previous harmaline+cactus tea trips. I'll examine this combo further.

I proceeded to repeat that dose several times, and did a whole series of higher strength trips. Two thirds the way through that I switched from harmaline/harmine to pure harmine because so much harmaline just feels debilitating.

Start low, pay attention, and keep notes.
You've got all the time in the world to shatter reality and become a rainbow :lol:

 

[0_o]

The advantages potentially lay in the applications.
Less is more applies potentially towards some uses.
The traditional uses of cactus and yage separately may have some common aspects.

If your intentions for using them involve an objective or specific goal then the combination may hold promise. However this isn't the kind of stuff that just happens when you take it and it isn't exactly public knowledge though it isn't exactly secret. I don't think it benefits anyone to openly discuss such things. Not everything is best laid out on the table... or mesa.

 

[Asher7]

@ Grey Fox, the main interest is using as little cacti material as possible. Maximum efficiency because of rarity and also knowing the characteristics since in my experience there can be a wide range of effect profiles. Second would be enhancement of an aspect like mentioned, cerebral clarity, sedation for better drifting. Long story short though it’s just plain curiosity.

@ Elrik, that’s actually a really good point, keeping the inhibitor consistent. I was thinking one step safer would be to not even worry about effects at first and just see if the two mixed cause any issues sitting in the gut. Once active levels are reached, definately wise to keep the maoi consistent.

@ 0_o, I’m not 100% sure what you mean. Are you suggesting we shouldn’t bring up the topic of harmalas + cacti due to possible backlash from another?

 

[Brennendes Wasser]

What I dont get:

Phenylethylamines (MDMA, Speed, Meth, 2C-B, ...) should NEVER be used with Harmalas.

And Meskaline is a Phenylethylamine. So why do people use it?

Why is it safe (at least I simply assume it because of people combining it) whereas ALL OTHER PEAs cause a deadly serotonine syndrom?

 

[Grey Fox]

Thanks for clearing that up Asher7. I get it now. Please keep updating us on how things go on future attempts.

Elrik that info you provided is really helpful. Thanks for sharing that.

suddenly you go from speaking with great clarity to speaking in a cryptic manner. If you have special insight that you would rather not share, then so be it. Why discourage others from sharing their insights?

 

[Asher7]

What I dont get:

Phenylethylamines (MDMA, Speed, Meth, 2C-B, ...) should NEVER be used with Harmalas.

And Meskaline is a Phenylethylamine. So why do people use it?

Why is it safe (at least I simply assume it because of people combining it) whereas ALL OTHER PEAs cause a deadly serotonine syndrom?

That was exactly my thinking as well8)

I don’t know, if anyone is thinking of taking a crack at it I would say start light because given the above quoted train of thought it would explain plain as day why I got so sick. Really all I can offer is, looks like we have an example of it possibly causing sickness and one where no “negative” happened. So, I’m not smart enough to draw a definate conclusion.

I will say this though. For a long time now all my attemtps at these things have been sorta pushing me away and I keep getting this sense that there is nothing else to “talk about”, like it’s taught me it’s lessons and now it’s time to apply it to our “real world”. Chances are it will be a few years before I try this combo again so, I’m just gonna save my insides and sit back and watch any possible real research, instead of fumbling blind and potentially bending something that can’t be unbent as Shulgin would say. It’s so much safer in theory just to stick to plain cacti and have the mental assurance that you are without doubt safe.

 

[Auxin]

Phenylethylamines (MDMA, Speed, Meth, 2C-B, ...) should NEVER be used with Harmalas.

Amphetamines should never be used with harmalas. Three of those four are amphetamines, not phenethylamines. Is unadulterated 2C-B proven to be dangerous in combination with harmalas?
Keep in mind that cacti contain more than just mescaline. So if harmalas are safe with cactus tea then it is safe with an assortment of phenethylamines and tetrahydroisoquinolines. People here and on other forums have posted about using peyote with harmalas and if I remember correctly, the non-mescaline alkaloids frequently outweigh mescaline itself in peyote.

 

[Grey Fox]

I’m just gonna save my insides and sit back and watch any possible real research, instead of fumbling blind and potentially bending something that can’t be unbent as Shulgin would say. It’s so much safer in theory just to stick to plain cacti and have the mental assurance that you are without doubt safe.

I think that is a good approach to take. The cacti by itself has a lot to offer and a great deal to explore in its own right.

 

[dreamer042]

Since there seems to be a lot of confusion here, some clarification would appear to be in order.

Phenethylamines are metabolized by MAO-B. Harmalas are reversible inhibitors of MAO-A with only very weak partial inhibition of MAO-B, and then only at very high doses.

It is possible that some cacti could contain serotonergic alkaloids, and individual sensitives are highly variable, so caution and basic harm reduction strategies (start low and work up, etc) always apply, but the anecdotal evidence of the hundreds of members of this forum who have safely experienced this combination suggest that (most of time, for most people) it's not a particularly dangerous combination.

This does not constitute a clean bill of health. This is still an underexplored combination and the potential for harm is still high. If one chooses to proceed with exploring this combination they do so at their own risk.

Know your body. Know your mind. Know your substance. Know your source.

 

[0_o]

My vague reply about applications and uses is about esoteric traditional practices that are not discussed much openly though one can find them mentioned in ethnobotanical literature.
I hinted at them with the play on words for table, the Mesa.
Telepathine was named so for a reason and cacti have also been used for such practices.
The word shaman gets thrown around a lot, but sorcery might be a bit more accurate though not particularly New Age friendly.
The uses include a wide variety of controversial phenomena.
Remote viewing, finding lost objects, out of body travel, spiritual attacks and defense against them, prophecy, evocations, invocations etc. I do not seek to encourage nor discourage, nor to provide support for or against the veracity of such things other than to say such practices exist.

I don't believe that the potentiation effects of harmala alkaloids are direct result or product of MAO inhibition. The effect of preventing DMT from being an MAO substrate renders it orally active, however many substances with MAO inhibiting properties do not appear to result in potentiation.

Harmala alkaloids have a complex range of biologically active properties. Among these is that they affect GABA receptors with a mild benzodiazepine like effect. This has an effect on glutamate an important and abundant neurotransmitter, a decrease in glutamate binding is associated with LSD tolerance and psychedelic effects involve both 5-HT2a and NMDA glutamate receptors.

And well then there is this:

Harmine, a natural beta-carboline alkaloid, upregulates astroglial glutamate transporter expression.
Li Y, et al. Neuropharmacology. 2011.

A rather useful receptor in the brain is the NMDA glutamate receptor.
Harmaline binds to it as a glutamate substitute and this causes an increase in glutamate through competitive enzymatic inhibition.
Other things that affects NMDA receptors are Nitrous Oxide, Ketamine and nicotine.
Interesting things happen with dopamine when you increase glutamate but not GABA. The brain speeds up in a way, and it feels good.

Anecdotal accounts suggest that drinking fruit juices with high levels of glutamic acid at the time of administration of a psychedelic causes a potentiation effect.

Those familiar with nitrous oxide and ketamine are familiar with their ability to potentiate psychedelic effects when taken during a a psychedelic experience.

Note that if tolerance to LSD is associated with decreased glutamate binding and cross tolerance between psychedelics is known to occur, then an increase in glutamate levels compensates for decreased binding, theoretically. If you have low tolerance this same effect on glutamate levels should potentiate psychedelic effects.

Several molecules with some degree of demonstrable MAO inhibitory effects do not appear to potentiate psychedelics, however numerous molecules that affect glutamate signal pathways and glutamate levels in the brain are known to potentate psychedelics.

Amphetamines are TAAR1 agonists and decrease dopamine neurotransmitter firing rates and thus likewise competitively inhibit enzymes and increase dopamine levels. The effects of TAAR1 agonists arise from their interaction with monoamine transmitters, like dopamine transmitters, however catecholamines (like dopamine) are monoamines and are used to regulate body temperature and blood pressure among other things.

It turns out D-amphetamine is a reversible MAO inhibitor.

But check this out:

Combining Stimulants and Monoamine Oxidase Inhibitors: A Reexamination of the Literature and a Report of a New Treatment Combination
Joshua A. Israel, MD
You can find that easily enough. It will surprise you.

Among the documented adverse reactions are hypertensive crisis, intracranial hemorrhage, hyperthermia, seizures etc. These are all associated with overdose on amphetamines.
Harmala alkaloids potentially compete with amphetamines(AMP) at enzymes that metabolise amphetamines, this theoretically alters their metabolism. By competing at enzymes with AMP harmala alkaloids increase the amount of free AMP in the body allowing its detrimental side effects to increase with symptoms strongly resembling overdose. This is ironic in a sad way as that because amphetamine is a MAO inhibitor and a TAAR1 agonist an overdose of it is essentially a negative side effect resulting from taking a MAO-i and a stimulant together!

Amphetamines are technically phenethylamines (PEA), however they are alpha methyl PEAs. Alpha methyl groups can similarly be added to tryptamine and it protects the molecule from MAO. Mescaline lacks an alpha methyl group and unlike it's alpha-methyl counterpart 3,4,5-trimethoxyamphetamjne the dose required for psychedelic effects from mescsline comparatively high, however it is also safe to take in large amounts, a large dose of mescaline is not associated with any negative side effects, (however I have experienced severe headaches and elevated bloodpressure from a massive dose of strong pachanoi combined with PC. It was extremely debilitating and I thought my life was in danger. I do not suspect mescaline was to blame. Tyramine and it's ring methoxylated counterparts are active TAAR1 agonists however mescaline is not.)

Check out:
Pharmacology of human trace amine-associated receptors: Therapeutic opportunities and challenges☆
Mark D.Berrya Mohammed Shahide


There is another aspect to consider... amphetamines cause an increase in catecholamines, these are normally broken down by various enzymes including MAO, by binding to MAO the harmala alkaloids should impact the metabolism of catecholamines used to regulate things like heart rate, body temp etc. Harmala alkaloids do affect catecholamine metabolism theoretically however they do not cause a large increase in catecholamine levels like TAAR agonists do so there is no real risk of harm from harmaloids. However if you read the paper about combining stimulants and MAO you know that the risks may be exaggerated in some cases and that negative effects from such combinations may be dose dependant.

So...
Harmala alkaloid potentiation from its affects on glutamate and not MAO inhibition.

Toxicity of MAO inhibitors and TAAR1 agonists when combined (at certain doses) mimics TAAR1 overdose. Tyramines and amphetamines are TAAR1 agonists but mescaline is not and it is safe in large doses quite unlike amphetamines, essentially toxic mescaline overdose is unheard-of. And amphetamines are also MAO inhibitors.

At least that's my take on this.

 

[pinkoyd]

People started investigating this question back in the '90s, mostly with investigational bioassays. No one back then had a bad reaction to the combination and I've never so much as heard of one in the intervening years. The papers cited seem to give a theoretical framework where we can say perhaps this combination is safe but 20+ years of experience would tend to argue that it is most probably so.

Personally I don't see an issue here. I've done it more than several times and the results have never been less than marvelouos.

 

[Brennendes Wasser]

Since there seems to be a lot of confusion here, some clarification would appear to be in order.

Phenethylamines are metabolized by MAO-B. Harmalas are reversible inhibitors of MAO-A with only very weak partial inhibition of MAO-B, and then only at very high doses.

So that means that ONLY the Amphetamines - which are a suborder of the Phenylethylamines - can be deadly as they will be affected by the MAO-Inhibition, causing a possible Serotonine Syndrom.

Ok if it is this way, then let it be. But then the next question comes up:

If the Mescaline (as a Phenylethylamine is not even metabolized by the inhibited MAO-Enzyme, then why even take it in combination? It would be like combining Coffe with MAOI xD

Therefore the whole reason of MAOI-Ingestion would fall apart as you will not enlarge the Mescaline Effect whatsoever.


The only thing I may come across now on my own: As Cacti have a mixture of psychoactive ingredients, then maybe some others are strengthened, which are NOT causing deadly serotonine syndroms.

But now to this date if someone is talking about Cacti then there is always only the focus on mescaline, as mescaline is by far the most prominent ingredient.

If it WOULD be that way that those other ingredients get fortified, then I would imagine that the effects should only be weak, as you will only adress the really minor components of that mixture O:

Is this true or is there another reason why the MAOI have an effect at all.

 

[Asher7]

Part of me wants to think that if there was clear merit to the harmalas enhancing the effects it would probably be as common to find reports of it as the lemon tek, or harmalas with mushrooms. Maybe less actually in the same proportion as it seems fewer people take cacti than mushrooms, but it’s not some hard to conceive combo that only a few would think to consider.

Any history in South America of the locals mixing any maoi with their cacti? I think tobacco is but I probably wouldn’t consider it in the same league as what we’re looking for.

 

[Auxin]

Wasser, harmalas are not magic-bullet RIMAs. They have their own psychoactive effects which can hypothetically synergize with other drugs and in addition to blocking MAO, harmalas are inhibitors of various CYP metabolic enzymes, including 3A4 and 2D6- two enzymes involved in phenethylamine metabolism, if I recall correctly.
All that is theory, the answer to why is that people find it works

Asher, Cimora is a broad term for cactus brew involving admixtures. One optional admixture that is reportedly traditional in some cimora brews is caapi

 

[0_o]

So that means that ONLY the Amphetamines - which are a suborder of the Phenylethylamines - can be deadly as they will be affected by the MAO-Inhibition...

Amphetamines are MAO inhibitors.:surprised

But wait! There's more!


Combining Stimulants and Monoamine Oxidase Inhibitors: A Reexamination of the Literature and a Report of a New Treatment Combination
Joshua A. Israel, MD

 

[pete666]

Pure harmala HCl extract has zero synergistic effect with pure mescaline HCl extract in my experience.
Harmalas : 100mg oral 30-40 minutes before mescaline plugged. Then another 100mg harmalas 45 minutes after mescaline.
The same harmalas dose is not psychedelic, but fully inhibiting in case of dmt for me.

 

[0_o]

Combining stimulants with monoamine oxidase inhibitors: a review of uses and one possible additional indication.
Feinberg SS. J Clin Psychiatry. 2004.

Combination therapy with monoamine oxidase inhibitors and other antidepressants or stimulants: strategies for the management of treatment-resistant depression.
Thomas SJ, et al. Pharmacotherapy. 2015

Two more papers worth reading.


I always take the harmala alkaloid at the same time as the cactus or alkaloid salt.
Predosing doesn't work to potentiate for me. I want them to be at the receptor sites at the same time.

 

[0_o]

From one of the papers I provided refs for

Two early case reports23,24 documented severe reactions to the combination of stimulants and MAOIs. A report from 196523 described a case of hypertensive crisis and cerebral hemorrhage from the combination of dextroamphetamine and phenelzine. A case from 196924 reported nonfatal hyperpyrexia after combined treatment with dextroamphetamine and tranylcypromine.

Later cases have documented more successful treatment with this medication combination. Feighner and colleagues25 treated a series of 13 patients with treatment-resistant MDD using either dextroamphetamine or methylphenidate along with an MAOI and found the combination safe and effective, with hypotension the most common adverse effect. Fawcett and colleagues26 treated a series of 32 patients with treatment-resistant MDD with either pemoline up to 112.5 mg/d or dextroamphetamine up to 40 mg/d in combination with tranylcypromine, phenelzine, isocarboxazid, or pargyline (pemoline and pargyline are no longer manufactured). They, too, found the combination to be effective and medically safe, with no episodes of hypertensive crisis.26 Three other case reports have documented safe and effective use of combining MAOIs and stimulants: 1 using dextroamphetamine 10 mg/d combined with tranylcypromine 40 mg/d for treatment-resistant MDD,27 1 combining methylphenidate 40 mg/d and moclobemide 600 mg/d for comorbid MDD and ADHD,28 and another using phenelzine 45 mg/d and methylphenidate 17.5 mg/d for comorbid MDD and ADHD.29 Feinberg30 reported a successful case of treatment of MDD and ADHD using the combination of tranylcypromine 50 mg/d and methylphenidate 45 mg/d, again with no adverse medical outcomes. A less favorable medical outcome was documented by Bodner et al,31 who reported the case of a patient who developed serotonin syndrome while being treated with the combination of isocarboxazid 30 mg/d, trazodone 150 mg/d, and methylphenidate 10–20 mg/d, although it was not possible to determine to what degree, if any, the stimulant was a factor in this adverse event.

Thomas et al32 provide a thorough review of the literature on combining MAOIs with potentially contraindicated medications for treatment-resistant MDD, including SSRIs and stimulants. Their review includes the only published case to date on use of the transdermal selegiline patch with an MAOI, reporting 1 case of safe and beneficial treatment using the selegiline transdermal patch 12 mg/d along with amphetamine. This review32 also includes a case using phenelzine 60 mg/d with methylphenidate (as well as desipramine 75 mg/d and trazodone 300 mg/d) that resulted in hypotension and tachycardia.

The claim that harmala alkaloids and amphetamines are potentially deadly is a claim I am having difficulty providing evidence for.
Can someone help me find a case where amphetamine and harmine resulted in a death?

 

[pete666]

I always take the harmala alkaloid at the same time as the cactus or alkaloid salt.
Predosing doesn't work to potentiate for me. I want them to be at the receptor sites at the same time.

This is what I am aiming too. Rectal ROA is much faster than oral and harmalas don't like going the same way as mesc and vice versa. I start to feel both +- at the same time